High-risk cytogenetics and extramedullary disease may be associated with worse outcomes after chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed or refractory multiple myeloma, according to data published in Haematologica.
Researchers found evidence to suggest that high-risk cytogenetics and extramedullary disease are associated with inferior progression-free survival (PFS) and overall survival (OS) after CAR T-cell therapy.
These findings come from a meta-analysis of 17 CAR T-cell therapy trials including 723 patients with relapsed/refractory, high-risk multiple myeloma. The patients’ median age was 59 years. They had received a median of 5 prior therapies, including autologous stem cell transplant in 51% of patients.
BCMA was the most frequent single target of CAR T-cell therapy. There were 2 trials of CAR-T cells targeting both BCMA and CD38 and 2 trials of CARs targeting both BCMA and CD19. There was 1 trial of a CAR targeting CD19 only.
The researchers found that extramedullary disease was not significantly associated with overall response rate (risk ratio [RR], 0.97; 95% CI, 0.92-1.02; P =.26) or minimal residual disease (MRD) status (RR, 0.93; 95% CI, 0.73-1.19; P =.84) after CAR T-cell therapy. The quality of this evidence was moderate. On the other hand, extramedullary disease was associated with worse PFS (RR, 1.44; 95% CI, 1.24-1.67; P <.001) and OS (RR, 1.96; 95% CI, 1.48-2.58; P <.001).
The researchers also found that high-risk cytogenetics were associated with worse overall response rate (RR, 0.86; 95% CI, 0.76-0.97; P =.01), but the quality of this evidence was low. In addition, having high-risk cytogenetics was associated with inferior PFS (RR, 1.70; 95% CI, 1.29-2.25; P <.001) and OS (RR, 2.11; 95% CI, 1.27-3.52; P =.004).
“[H]igh-risk cytogenetics were significantly associated with worse outcomes after CAR T-cell therapy,” the researchers concluded. “Although EMD [extramedullary disease] showed promising initial response rates including MRD, risk for relapse and mortality was significantly increased. [T]he results of this analysis should be interpreted with caution and underscore future research into mechanisms of relapse, design of innovative treatment sequencing studies, and careful follow-up of these patients even after initial response.”
Gagelmann N, Ayuk FA, Klyuchnikov E, Wolschke C, Berger SC, Kröger N. Impact of high-risk disease on efficacy of CAR-T cell therapy for multiple myeloma: A meta-analysis of 723 patients. Haematologica. Published online February 23, 2023. doi:10.3324/haematol.2022.282510